The use of fixed combinations in acne vulgaris (acne) is very common, however comparative clinical trial data are limited. Cutaneous tolerability can influence patient compliance, and concerns about skin irritation with topical acne treatments have lead to a number of comparative split-face studies. Recently, a new fixed combination product was introduced (clin 1.0%-BP 3.75% gel) that was shown to be effective in reducing both inflammatory and noninflammatory lesions in moderate to severe acne. Here, we assess the tolerability of clin 1.0%-BP 3.75% gel compared with adap 0.1%-BP 2.5% gel in healthy volunteers with no apparent facial redness or dryness over 21-days, using a split-face methodology. Especially over the first two weeks of treatment, clin 1.0%-BP 3.75% gel was more tolerable than adap 0.1%-BP 2.5% gel, with statistically significant differences in cumulative change from baseline starting as early as day 8 (dryness) and day 9 (erythema), and composite index on days 8-12 and 16. Transepidermal water loss was less with clin 1.0%-BP 3.75% gel, although the difference was not statistically significant.